Cytoneme-mediated transport of active Wnt5b-Ror2 complexes in zebrafish.

Cytoneme-mediated transport of active Wnt5b-Ror2 complexes in zebrafish.
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DOI:
10.1038/s41586-023-06850-7
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发表时间:
2024-01
期刊:
影响因子:
64.8
通讯作者:
Scholpp, Steffen
Scholpp, Steffen
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Zhang, Chengting;Brunt, Lucy;Ono, Yosuke;Rogers, Sally;Scholpp, Steffen

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化学信号是胚胎中细胞交流的主要手段。基本原理是指一组产生配体的细胞和一组对该信号作出反应的细胞,因为它们表达了适当的受体。在斑马鱼胚胎中,Wnt5b与受体Ror2结合,触发wnt -平面细胞极性(PCP)信号通路,调节组织极性和细胞迁移。然而,目前尚不清楚这种亲脂性配体是如何通过水胞外空间从源细胞转运到靶组织的。在这项研究中,我们提供了证据,证明Wnt5b和Ror2一起装载在称为细胞素的长突起上。我们的数据进一步表明,活性Wnt5b-Ror2复合物在产生细胞中形成,并从这些细胞素传递给接收细胞。然后,无论Ror2受体的功能状态如何,接收细胞都有能力启动Wnt-PCP信号。在组织水平上,我们进一步表明,活性Wnt5b-Ror2的细胞素依赖性扩散影响斑马鱼原肠胚中的收敛和延伸。我们认为细胞素介导的配体受体复合物的转移是旁分泌信号传导的重要机制。这可能会促使人们重新评估仅根据受体表达来表征反应性和非反应性组织的传统概念。在斑马鱼胚胎中,Wnt5b及其膜结合受体Ror2的活性复合物通过称为细胞素的细胞突起在细胞之间运输,在不内源性表达该受体的细胞中启动旁分泌Wnt5b信号传导。
Chemical signalling is the primary means by which cells communicate in the embryo. The underlying principle refers to a group of ligand-producing cells and a group of cells that respond to this signal because they express the appropriate receptors. In the zebrafish embryo, Wnt5b binds to the receptor Ror2 to trigger the Wnt–planar cell polarity (PCP) signalling pathway to regulate tissue polarity and cell migration. However, it remains unclear how this lipophilic ligand is transported from the source cells through the aqueous extracellular space to the target tissue. In this study, we provide evidence that Wnt5b, together with Ror2, is loaded on long protrusions called cytonemes. Our data further suggest that the active Wnt5b–Ror2 complexes form in the producing cell and are handed over from these cytonemes to the receiving cell. Then, the receiving cell has the capacity to initiate Wnt–PCP signalling, irrespective of its functional Ror2 receptor status. On the tissue level, we further show that cytoneme-dependent spreading of active Wnt5b–Ror2 affects convergence and extension in the zebrafish gastrula. We suggest that cytoneme-mediated transfer of ligand–receptor complexes is a vital mechanism for paracrine signalling. This may prompt a reevaluation of the conventional concept of characterizing responsive and non-responsive tissues solely on the basis of the expression of receptors. In zebrafish embryos, active complexes of Wnt5b and its membrane-bound receptor Ror2 are transported between cells via cellular protrusions called cytonemes to initiate paracrine Wnt5b signalling in cells that do not endogenously express the receptor.
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